1. Field of the Invention
This invention relates to new methods and compounds for determining lithium level in serum or other samples suspected of containing lithium, and more particularly to a homogeneous colorimetric method that is performed directly on the sample without deproteinization. Lithium in the form of lithium carbonate is administered to manic-depressive patients. The therapeutic range of lithium ion in plasma is quite narrow, namely, 0.8 to 1.2 mM. It is important to monitor the lithium level in such patients because of the toxic side effects that appear when the lithium level in blood exceeds the recommended level.
Current methods for detecting and determining lithium generally involve flame emission or atomic absorption methods. These techniques are disadvantageous because they are slow and labor intensive.
2. Description of the Related Art
Recently, colorimetric tests have been suggested for lithium analysis. R. V. Sitnikova et al in Zh. Anal. Khim., 37(4) 611-13(1982) disclose use of TMC-crownformazan (15, 16-dihydro-7-cyano-5H, 17H-dibenzo [b,i] [1,11,4,5,7,8]-dioxa-tetraazacyclotetradecine) as a reagent to complex lithium. A spectometric method for determining lithium in plasma and urine was suggested using either the aforementioned crownformazan or a pyrazolone by R. V. Sitnikova et al in Lab. Delo. (3) 142-5(1980).
Use of TMC-crownformazan in lithium assays is disadvantageous. Such tests require the use of nearly water-free organic solvents, and therefore require that the sample be pretreated to remove protein which otherwise precipitates in the organic solvents and interferes with the assay. Further, only slight chromophoric changes are observed when crownformazan is used to complex lithium ion. Pyrazolones have been found to be both less selective and less sensitive than TMC-crownformazan. Further, tests using pyrazolones require deproteinization.
Use of an arsenophenyl ligand called Thoron in an alkaline acetone medium has been suggested by J. K. Trautman et al in Talanta 30(8) 587-91 (1983) for spectrophotometric determination of lithium. The dye solution suggested by Trautman et al is disadvantageous because it has a short shelf life, and sodium and other ions interfere with the results. Additionally, lithium assays using Thoron require deproteinization.